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      Heart failure hospitalization risk associated with use of two classes of oral antidiabetic medications: an observational, real-world analysis

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          Abstract

          Background

          Newer oral antidiabetic drug classes are expanding treatment options for type 2 diabetes mellitus (T2DM); however, concerns remain. The objective was to assess relative risk of heart failure hospitalization of sodium–glucose co-transporter-2 (SGLT2) and dipeptidyl peptidase-4 (DPP4) inhibitors in T2DM patients.

          Methods

          This retrospective observational study used a national commercially insured claims database. Adults (>18 years) with T2DM newly starting SGLT2 or DPP4 medication between April 2013 and December 2014 were included. Depending on their index fill, patients were grouped into either SGLT2 or DPP4 medication class cohorts. The primary outcome was hospitalization for heart failure and the risk was assessed using Cox regression models. Propensity score matching (1:2 ratio) was used to adjust for potential confounders. Analyses were also stratified by the presence of baseline diabetes complication and age (<65 vs 65+).

          Results

          The matched cohort included 4899 SGLT2 and 9798 DPP4 users. The risk of heart failure hospitalization was lower among SGLT2 users in comparison with matched DPP4 users (2.0% SGLT2 vs 3.1% DPP4; adjusted hazard ratio [aHR] 0.68; 95% confidence interval [CI] 0.54–0.86; p = .001). However, the stratified analyses revealed no risk difference among the majority of the analyzed patients, i.e., those aged <65, which comprised 85% of the matched cohort (aHR = 0.78; 95% CI 0.57–1.05; p = .09), and those without prior complication, which comprised 69% of matched cohort (aHR = 0.83; 95% CI 0.54–1.27; p = 0.40).

          Conclusions

          In this real-life analysis, the rate of hospitalizations for heart failure was significantly lower for patients initiating an SGLT2 compared with a DPP4 medication, specifically among older patients and those with diabetes complication.

          Electronic supplementary material

          The online version of this article (doi:10.1186/s12933-017-0575-x) contains supplementary material, which is available to authorized users.

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          Most cited references23

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          Marginal structural models to estimate the causal effect of zidovudine on the survival of HIV-positive men.

          Standard methods for survival analysis, such as the time-dependent Cox model, may produce biased effect estimates when there exist time-dependent confounders that are themselves affected by previous treatment or exposure. Marginal structural models are a new class of causal models the parameters of which are estimated through inverse-probability-of-treatment weighting; these models allow for appropriate adjustment for confounding. We describe the marginal structural Cox proportional hazards model and use it to estimate the causal effect of zidovudine on the survival of human immunodeficiency virus-positive men participating in the Multicenter AIDS Cohort Study. In this study, CD4 lymphocyte count is both a time-dependent confounder of the causal effect of zidovudine on survival and is affected by past zidovudine treatment. The crude mortality rate ratio (95% confidence interval) for zidovudine was 3.6 (3.0-4.3), which reflects the presence of confounding. After controlling for baseline CD4 count and other baseline covariates using standard methods, the mortality rate ratio decreased to 2.3 (1.9-2.8). Using a marginal structural Cox model to control further for time-dependent confounding due to CD4 count and other time-dependent covariates, the mortality rate ratio was 0.7 (95% conservative confidence interval = 0.6-1.0). We compare marginal structural models with previously proposed causal methods.
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            Lower Risk of Heart Failure and Death in Patients Initiated on Sodium-Glucose Cotransporter-2 Inhibitors Versus Other Glucose-Lowering Drugs

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              The epidemiology of heart failure: The Framingham Study

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                Author and article information

                Contributors
                302-230-2023 , sgautam@healthcore.com
                aagiro@healthcore.com
                jbarron@healthcore.com
                powert@aimspecialtyhealth.com
                harry.weisman@anthem.com
                jeff.white@anthem.com
                Journal
                Cardiovasc Diabetol
                Cardiovasc Diabetol
                Cardiovascular Diabetology
                BioMed Central (London )
                1475-2840
                31 July 2017
                31 July 2017
                2017
                : 16
                : 93
                Affiliations
                [1 ]ISNI 0000 0001 0698 1725, GRID grid.467616.4, , HealthCore, Inc., ; 123 Justison St, Suite 200, Wilmington, DE 19801 USA
                [2 ]AIM Specialty Health, Chicago, IL USA
                [3 ]ISNI 0000 0001 0698 1725, GRID grid.467616.4, , Anthem, Inc., ; Indianapolis, IN USA
                Article
                575
                10.1186/s12933-017-0575-x
                5535291
                28756774
                fbc7e9d5-c4b6-42d8-981e-692e96aa3f04
                © The Author(s) 2017

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 8 June 2017
                : 21 July 2017
                Funding
                Funded by: Anthem, Inc.
                Categories
                Original Investigation
                Custom metadata
                © The Author(s) 2017

                Endocrinology & Diabetes
                sglt2,dpp4,type 2 diabetes,oad,heart failure,claims analysis
                Endocrinology & Diabetes
                sglt2, dpp4, type 2 diabetes, oad, heart failure, claims analysis

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